宫内发育迟缓大鼠胰腺肝脏骨骼肌中胰岛素受体底物的表达

目的 分析宫内发育迟缓(IUGR)大鼠胰腺、肝脏、骨骼肌中胰岛素受体底物1（IRS-1）和2(IRS-2) mRNA和蛋白水平的表达，探讨IUGR个体发生胰岛素抵抗的机制。方法 采用母孕期低蛋白饮食法建立IUGR大鼠模型，以模型鼠产下的仔鼠为IUGR组；以孕期予正常饮食母鼠产下的仔鼠为对照组。应用RT-PCR法检测各组仔鼠在出生后0、3和8周时点胰腺、肝脏和骨骼肌中IRS-1、IRS-2 mRNA表达水平，采用Western blot检测 IRS-1和IRS-2蛋白表达水平。检测3和8周时点仔鼠空腹血糖和血清胰岛素水平，计算胰岛素抵抗指数。结果 ①IUGR组出生后0和3周体重显著低于对照组；8周时点IUGR组体重显著高于对照组。②IUGR组出生后0、3和8周时点胰腺、肝脏IRS-2 mRNA和蛋白表达水平低于对照组；IRS-1 mRNA和蛋白表达水平与对照组差异无统计学意义；骨骼肌IRS-1 mRNA和蛋白表达水平均显著低于对照组；IRS-2蛋白表达水平与对照组差异无统计学意义。③至8周时点，骨骼肌IRS-1 mRNA和蛋白表达水平的下降幅度较胰腺和肝脏组织更为明显；肝脏IRS-2 mRNA和蛋白表达水平的下降幅度较胰腺和骨骼肌组织更为明显。④至8周时点，IUGR组空腹血糖水平与对照组差异无统计学意义，胰岛素水平和空腹胰岛素抵抗指数较对照组显著升高。结论 IUGR大鼠胰腺、肝脏和骨骼肌组织均存在IRS-1或IRS-2 mRNA和蛋白表达水平的下降，可能是发生胰岛素抵抗的机制之一。

Expression of insulin receptor substrates of pancreas, liver and skeletal muscle in intrauterine growth retardation rats

Objective To analyze the expression of insulin receptor sustrate 1 (IRS-1) and 2 (IRS-2) mRNAs and proteins of pancreas, liver and skeletal muscle tissue of intrauterine growth retardation (IUGR) rats, and to investigate the mechanism of insuline resistance development. Methods IUGR model was established by using gestational low-protein diet method. The model rats were then randomly divided into IUGR group and control group (receiving regular diet during pregnancy). IRS-1 and IRS-2 mRNAs were detected in pup rat pancreas, liver and skeletal muscle at 0, 3 and 8 weeks after birth. At the same time, the expressions of IRS-1 and IRS-2 proteins were examined with Western blot method. Fasting blood glucose, serum insulin levels were tested in pup rats at 3 and 8 weeks after birth, and insulin resistance index was calculated. Results ① The mean birth weight and body weight at the 3rd week of pup rats in IUGR group were significantly lower than that in control, whereas it reversed at the 8th week. ② The IRS-2 mRNA and protein expression levels among pancreas and liver tissue of IUGR group were lower than those of control group. There was no significant difference in IRS-1 mRNA and protein expression levels between IUGR and control groups. Skeletal muscle IRS-1 mRNA and protein expression levels at each time point were lower than those of control group. IRS-2 protein expression levels of IUGR group did not differ from control group. ③ Skeletal muscle IRS-1 mRNA and protein expression level decreased more than pancreas and liver at the 8th week. Liver IRS-2 mRNA and protein expression level decreased more than pancreas and skeletal muscle. ④ There was no signigicant difference in blood glucose between IUGR and control groups at the 8th week. The level of insulin and FIRI in IUGR group increased more than that in control group. Conclusions The IRS-1 and IR-2 mRNA and protein expression in pancreas,peripheral tissue and liver declined , with most significant decline in liver. It may be one of the mechanisms of insulin resistance.